The primary objective of the research to be supported by this ADAMHA Scientist Development Award is the characterization of changes in gene expression in the nucleus accumbens of the adult rat brain induced by chronic cocaine and opiate administration. Addiction resulting from self-administration of several classes of drugs requires intact neuronal connections within the nucleus accumbens. Identification of messenger (m) RNA molecules regulated by both cocaine and morphine will be helpful in isolating the proteins which underlay the biological basis of the self-administration of addictive drugs. Specifically, this project will consist of three sections: i) the identification of cocaine-and morphine-regulated mRNAs from tissue sections containing the nucleus accumbens that encode proteins involved in signal transduction; ii) the isolation and characterization of novel mRNA from the nucleus accumbens regulated by cocaine or morphine administration; and iii) the description of the neurotransmitter receptor mRNA composition of individual dopaminergic neurons studied in live slice preparations of the nucleus accumbens. Techniques will be applied which enrich the mRNAs of interest via both in situ transcription in fixed tissue sections and patch clamp studies of live single neurons. Identification and characterization of known and novel drug-regulated mRNAs will lead to future studies investigating the functional role of the proteins encoded by these mRNAs in cocaine and morphine self- administration. The treatment of drug addiction is limited by an incomplete understanding of the molecular mechanisms underlying repeated drug use. Identification of mRNAs regulated by both cocaine and morphine in the rat will highlight factors common to many forms of drug addiction.